Search

Using a model of coronary heart disease incidence based on multivariate logistic regression functions from the Framingham Heart Study, the cost effectiveness of simvastatin was compared with that of cholestyramine in preventing such disease. For men with initial cholesterol levels of 310 mg/dl, the cost effectiveness of cholestyramine, expressed in Dutch guilders, ranges from approximately 220,000 to 510,000 guilders per year of life saved, depending on age at initiation of therapy. For simvastatin, cost-effectiveness ratios range from 50,000 to 110,000 guilders per year of life saved among this group of men. Results are similar for women, although the cost effectiveness of both agents is considerably less. These results suggest that simvastatin is substantially more cost effective than cholestyramine; that it compares well with other generally accepted medical practices, especially if therapy is initiated at an early age; and that simvastatin should become accepted as a drug of first choice in the treatment of persons with elevated serum cholesterol levels as its long-term safety record becomes more established.

The effects of synvinolin (MK-733), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, were investigated in 43 patients with heterozygous familial hypercholesterolaemia in a double-blind, placebo-controlled, dose-finding study. Synvinolin was given in doses ranging from 2.5 mg to 80 mg per day for 4 weeks. 8 patients received placebo. Low-density-lipoprotein cholesterol fell on average by 18% on 2.5 mg/day and 42% on 80 mg/day. The drug was as effective whether it was given once or twice daily. Serum high-density-lipoprotein cholesterol tended to increase and serum triglycerides to decrease on the higher doses. The drug was tolerated well. Except for a slight rise in alanine aminotransferase in 3 patients no objective side-effects were observed.

By the combination of boronate affinity chromatography on micro columns and immunoturbidimetry, a method was developed for the measurement of glycated apoliprotein B (Apo-B). The overall precision of the method was 11%. The sensitivity was 0.3 mg/l Apo-B or 0.05% glycated Apo-B, which is far below physiological levels. The recovery after column separation was 95 +/- 7%. In vitro incubation of plasma with 90 mmol/l D-glucose showed an increase in the percentage glycated Apo-B of 0.58% per hour. The simplicity of the method makes it suitable for screening purposes. Non-diabetic patients (n = 21) and diabetic patients (n = 35) were screened for glycated and total Apo-B. Total Apo-B in diabetics (1.02 +/- 0.53 g/l) was increased (controls: 0.75 +/- 0.18 g/l; p less than 0.05) and a positive correlation between HbA1 and Apo-B (r = 0.36, p less than 0.05) was present in this group. However, no significant difference of glycated Apo-B was measured between diabetics and controls (10.4 +/- 2.8 and 11.5 +/- 1.4%, respectively). The possible implications of these findings are discussed.

Alimentary lipemia stimulates the transfer of cholesteryl ester between lipoproteins in vitro and may alter lipoprotein cholesteryl ester distribution in vivo. The effect of a single, large oral fat load on lipoprotein cholesteryl ester redistribution and the activity of cholesteryl ester transfer protein was investigated in six normolipidemic men (Group A), six combined hyperlipidemic men (Group B), and six hypercholesterolemic men (Group C). Fasting triglyceride-rich lipoprotein cholesteryl ester was high in Group B, low in Group A, and intermediate in Group C (A less than C less than B, p less than 0.05). After an oral fat load, total plasma cholesteryl ester was unchanged in all groups. In Group A, cholesteryl ester increased in smaller triglyceride-rich lipoproteins and remained so at 24 hours. Conversely, low density and high density lipoprotein cholesteryl ester decreased and returned to fasting values at 24 hours. In Group B, cholesteryl ester increased in large triglyceride-rich lipoproteins. Low density and high density lipoprotein cholesteryl ester (expressed as percentage of plasma cholesteryl ester) decreased. By contrast, in Group C, triglyceride-rich lipoprotein and low density lipoprotein cholesteryl ester remained unaltered, and only high density lipoprotein cholesteryl ester decreased. The activity of cholesteryl ester transfer protein increased in all groups and returned to fasting values at 24 hours. No differences in response were observed among the three groups. It is concluded that an oral fat load can induce a shift in lipoprotein cholesteryl ester distribution from high and low density lipoproteins to triglyceride-rich lipoproteins without affecting total plasma cholesteryl ester.(ABSTRACT TRUNCATED AT 250 WORDS)

A parameter of peripheral insulin activity (A = 10(4)/IpGp) can be obtained after oral glucose loading by simple calcuation using insulin and glucose levels at the glucose peak. In combination with a glucose-independent parameter of beta-cell function (CIR = 100. I/G(G-70) a parameter of glucose tolerance (GT = A-CIR) is defined. The parameters allow one to separate the contributions of beta-cell function and peripheral insulin resistance to the glucose tolerance observed after glucose loading. Examples, based on the literature and our own work, illustrate the increase of A and GT by cortisone acetate premedication as well as long-term oral contraceptive medication.

From the dose-response relations between glucose and insulin after oral glucose loading, a reproducible parameter for beta-cell response was deduced. The main advantage of this parameter -corrected insulin response, defined as CIR = I- 100/G(G-70)- lies in it independence from the initial or reached glucose level.

Abetalipoproteinemia is characterized by the absence of chylomicrons, very low density and low density lipoproteins from the plasma. To study neutral lipid exchange between lipoproteins in vivo a chylomicron model, Intralipid R, was infused in an abetalipoproteinemic patient. During a three hour infusion of 250 mg/kg/hr after a priming dose of 100 mg/kg triglyceride, 8% of the triglyceride mass of Intralipid was replaced by cholesterolester, while 8% of the cholesterylester mass was replaced by triglyceride in high density lipoproteins. Thus, the exchange of cholesterylester and triglyceride between high density lipoprotein and triglyceride rich particles in vivo was directly demonstrated in the absence of apolipoprotein B.

The present study provides a histochemical analysis of the macromolecular and cellular composition of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) in the rat with special reference to the different types of lipids present and to the participation of monocytes. FSGHS was induced in male Wistar rats by unilateral nephrectomy (UN) or puromycin aminonucleoside (PAN) injections. Histochemical analysis of glomeruli with FSGHS in both models after 20 weeks of proteinuria revealed massive deposits of lipids. These lipid accumulations were shown to consist mainly of free and esterified cholesterol; triglycerides and phospholipids were present in small amounts. Monocytes, identified by the alpha-naphthyl acetate method for non-specific esterase activity were scanty in glomeruli affected by FSGHS with an average glomerular count of 0.1 in UN- and 0.2 in PAN-treated rats. When present, no preferential localization of monocytes in the lesions was observed. The progressive glomerular damage occurring once the process of hyalinosis and sclerosis has started may be related to the paucity of "scavenging" monocytes. Cholesterol may be one of the substances involved in the development of these glomerular changes.